Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics.

E Björnson,C J Packard,M Adiels,A Thorsell,J Borén,S Söderlund,L Andersson,J Kahri,H Zhou,N Matikainen,C Sihlbom,M.‐R Taskinen

doi:10.1111/joim.12877

Abstract

BackgroundTriglyceride‐rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low‐density lipoproteins (VLDL).MethodsMass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL 1 and VLDL 2 density intervals. An integrated non‐steady‐state multicompartmental model was constructed to describe the metabolism of apoB48‐ and apoB100‐containing lipoproteins following a fat‐rich meal, as well as during prolonged fasting.ResultsThe kinetic model described the metabolism of apoB48 in CM, VLDL 1 and VLDL 2. It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL 1 and VLDL 2. ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50 mg day−1, and the increment during absorption was about 230 mg day−1. The fractional catabolic rates for apoB48 in VLDL 1 and VLDL 2 were substantially lower than for apoB48 in CM.DiscussionThis novel non‐steady‐state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.

Highlights

Recent genetic and epidemiological studies have provided evidence that plasma triglyceride-rich lipoproteins (TRLs) play a causal role in cardiovascular disease, and this has prompted renewed interest in understanding better the metabolism of these lipoproteins and their potential contribution to atherogenesis [1,2,3]
The kinetic model described the metabolism of apoB48 in CM, VLDL1 and VLDL2
ApoB48 particles with a long residence time were present in very lowdensity lipoproteins (VLDL), and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions

Summary

Introduction

Recent genetic and epidemiological studies have provided evidence that plasma triglyceride-rich lipoproteins (TRLs) play a causal role in cardiovascular disease, and this has prompted renewed interest in understanding better the metabolism of these lipoproteins and their potential contribution to atherogenesis [1,2,3]. TRLs in the circulation are acted on first by lipoprotein lipase to remove much of the core triglyceride, and the resulting remnants are cleared by cell-surface receptors [4], or in the case of VLDL converted (in part) by further lipolysis to intermediate- and low-density lipoproteins These lipid metabolism pathways are quantitatively significant; during fasting conditions in healthy individuals, the liver releases about 20–70 g of VLDL triglyceride per day associated with about 1 g of apoB100, while the intestine absorbs and packages in the order of 50–200 g of triglyceride daily depending on the fat content of the diet [5, 6]. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very lowdensity lipoproteins (VLDL)

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Results

Conclusion